This proposal includes related studies in hamsters and humans with gallstones. The thrust of the studies in hamsters is the rapid evaluation of the efficacy and mechanism of action of agents that prevent or dissolve cholesterol gallstones. The thrust of the studies in humans is an evaluation of measures to enhance the dissolution of gallstones by ursodeoxycholic acid (UDCA) Hamsters receiving a low dose of ethinyl estradiol and 3-fold increase in dietary cholesterol produce saturated bile and cholesterol gallstones indistinguishable by scanning electron microscopy from cholesterol gallstones in humans. Chenodeoxycholic acid (CDCA) and UDCA but not cholic acid dissolve gallstones in humans and have been shown to prevent and dissolve gallstones in the hamsters. Other agents to be tested and compared to CDCA and UDCA in the hamster model include Rowachol and its individual terpene constituents, the lipophylic resin XAD-2 and epimers of CDCA and UDCA (3 beta, 7 beta; 3 beta 7 alpha) and 7 alpha cholanoic acid. Biliary lipid and bile acid composition, bile acid pool size and the rate limiting enzymes of the hepatic synthesis of bile acids and cholesterol will be determined. In the clinical trial the effects of a low cholesterol diet, bran and medium chain triglycerides on biliary lipid composition and on the rate of dissolution of gallstones by UDCA will be determined. Bile saturation, biliary lipid secretion, bile acid kinetics and serum lipoprotein profiles will be determined in the patients with gallstones before and after UDCA. In addition, the effect of increased dietary cholesterol on the saturation index of bile will be determined in patients with gallstones and matched controls.